title: 7-Substituted pterins. A new class of mammalian pteridines.
abstract: Three novel pteridines have been isolated from the urine of patients with a new variant of 6-(L-erythro-1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin (tetrahydrobiopterin) deficiency, showing hyperphenylalaninemia. From the results of high performance liquid chromatography, oxidative degradation, and gas chromatography-electron impact mass spectrometry, their structures were identified as 7-(D-erythro-1',2',3'-trihydroxypropyl)-pterin (7-neopterin), 7-(L-erythro-1',2'-dihydroxypropyl)-pterin (7-biopterin), and 6-oxo-7-(L-erythro-1',2'-dihydroxypropyl)-pterin (6-oxo-7-biopterin). The ratio of biopterin to 7-biopterin in the patients' urines was 1:1, and after oral loading with tetrahydrobiopterin, 7-biopterin excretion rose parallel to biopterin. This finding suggests that 7-substituted pterins may be formed endogenously by a yet unknown isomerization reaction. The cause of hyperphenylalaninemia is still unclear. The activities of the enzymes involved in tetrahydrobiopterin biosynthesis and regeneration were found to be normal in the patients, and no effect of 7-biopterin on these enzymes was observed in vitro. However, compared with the normal cofactor, tetrahydrobiopterin, the Km values of tetrahydro-7-biopterin for phenylalanine hydroxylase and dihydropteridine reductase are 20 and 5 times higher, respectively.
authors.affiliation: Department of Pediatrics, University of Zurich, Switzerland.
authors.forename: H C
authors.initials: HC
authors.lastname: Curtius
authors.forename: A
authors.initials: A
authors.lastname: Matasovic
authors.forename: G
authors.initials: G
authors.lastname: Schoedon
authors.forename: T
authors.initials: T
authors.lastname: Kuster
authors.forename: P
authors.initials: P
authors.lastname: Guibaud
authors.forename: T
authors.initials: T
authors.lastname: Giudici
authors.forename: N
authors.initials: N
authors.lastname: Blau
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004093:Dihydropteridine Reductase / Q000378:metabolism; D004912:Erythrocytes / Q000032:analysis; D006136:GTP Cyclohydrolase / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007202:Indicators and Reagents; D007536:Isomerism; D007962:Leukocytes / Q000032:analysis; D008099:Liver / Q000201:enzymology; D008297:Male; D010084:Oxidation-Reduction; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D011621:Pteridines / Q000097:blood / Q000494:pharmacology / Q000652:urine*; D011622:Pterins / Q000097:blood / Q000494:pharmacology / Q000652:urine*; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D011621:Pteridines; D011622:Pterins; D010651:Phenylalanine Hydroxylase; D004093:Dihydropteridine Reductase; D006136:GTP Cyclohydrolase